Prognostic Awareness and Goals of Care Discussions Among Patients With Advanced Heart Failure.

Background: Prognostic awareness (PA)-the understanding of limited life expectancy-is critical for effective goals of care discussions (GOCD) in which patients discuss their goals and values in the context of their illness. Yet little is known about PA and GOCD in patients with advanced heart failure (HF). This study aims to determine the prevalence of PA among patients with advanced HF and patient characteristics associated with PA and GOCD.

Early-Onset Familial Alzheimer Disease Variant PSEN2 N141I Heterozygosity is Associated with Altered Microglia Phenotype.

Background: Early-onset familial Alzheimer disease (EOFAD) is caused by heterozygous variants in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and APP genes. Decades after their discovery, the mechanisms by which these genes cause Alzheimer's disease (AD) or promote AD progression are not fully understood. While it is established that presenilin (PS) enzymatic activity produces amyloid-β (Aβ), PSs also regulate numerous other cellular functions, some of which intersect with known pathogenic drivers of neurodegeneration.

QALY-time: experts' view on the use of the quality-adjusted LIFE year in COST-effectiveness analysis in palliative care.

Background: The Quality-Adjusted Life Year (QALY) is internationally recognized as standard metric of health outcomes in cost-effectiveness analyses (CEAs) in healthcare. The ongoing debate concerning the appropriateness of its use for decision-making in palliative care has been recently mapped in a review. The aim was to report on and draw conclusions from two expert meetings that reflected on earlier mapped issues in order to reach consensus, and to advise on the QALY's future use in palliative care.

Differences in Staff-Assessed Pain Behaviors among Newly Admitted Nursing Home Residents by Level of Cognitive Impairment.

Objective: Pain is common among nursing home residents with cognitive impairment and dementia. Pain is often underdiagnosed and undertreated, which may lead to adverse health outcomes. Nonverbal behaviors are valid indicators of pain, but the extent to which these behavioral expressions vary across levels of cognitive impairment is unknown.

Evaluation of a Novel Educational Intervention to Improve Conversations About Implantable Cardioverter-Defibrillators Management in Patients with Advanced Heart Failure.

Implantable cardioverter-defibrillators (ICDs) reduce the incidence of sudden cardiac death for high-risk patients with heart failure (HF), but shocks from these devices can also cause pain and anxiety at the end of life. Although professional society recommendations encourage proactive discussions about ICD deactivation, clinicians lack training in conducting these conversations, and they occur infrequently. As part of a six-center randomized controlled trial, we evaluated the educational component of a multicomponent intervention shown to increase conversations about ICD deactivation by clinicians who care for a subset of patients with advanced HF.

Analysis of Immune Checkpoint Drug Targets and Tumor Proteotypes in Non-Small Cell Lung Cancer.

New therapeutics targeting immune checkpoint proteins have significantly advanced treatment of non-small cell lung cancer (NSCLC), but protein level quantitation of drug targets presents a critical problem. We used multiplexed, targeted mass spectrometry (MS) to quantify immunotherapy target proteins PD-1, PD-L1, PD-L2, IDO1, LAG3, TIM3, ICOSLG, VISTA, GITR, and CD40 in formalin-fixed, paraffin-embedded (FFPE) NSCLC specimens. Immunohistochemistry (IHC) and MS measurements for PD-L1 were weakly correlated, but IHC did not distinguish protein abundance differences detected by MS.

Oligomeric collagen as an encapsulation material for islet/β-cell replacement: effect of islet source, dose, implant site, and administration format.

Replacement of islets/β-cells that provide long-lasting glucose-sensing and insulin-releasing functions has the potential to restore extended glycemic control in individuals with type 1 diabetes. Unfortunately, persistent challenges preclude such therapies from widespread clinical use, including cumbersome administration via portal vein infusion, significant loss of functional islet mass upon administration, limited functional longevity, and requirement for systemic immunosuppression. Previously, fibril-forming type I collagen (oligomer) was shown to support subcutaneous injection and in situ encapsulation of syngeneic islets within diabetic mice, with rapid (<24 h) reversal of hyperglycemia and maintenance of euglycemia for beyond 90 days.

Embedded model discrepancy: A case study of Zika modeling.

Mathematical models of epidemiological systems enable investigation of and predictions about potential disease outbreaks. However, commonly used models are often highly simplified representations of incredibly complex systems. Because of these simplifications, the model output, of, say, new cases of a disease over time or when an epidemic will occur, may be inconsistent with the available data.

A limited range of vagus nerve stimulation intensities produce motor cortex reorganization when delivered during training.

Pairing vagus nerve stimulation (VNS) with rehabilitation has emerged as a potential strategy to improve recovery after neurological injury, an effect ascribed to VNS-dependent enhancement of synaptic plasticity. Previous studies demonstrate that pairing VNS with forelimb training increases forelimb movement representations in motor cortex. However, it is not known whether VNS-dependent enhancement of plasticity is restricted to forelimb training or whether VNS paired with other movements could induce plasticity of other motor representations.

Oral bacterial diversity is inversely correlated with mucosal inflammation.

Objective: We investigated the relationship amongst the oral mucosal bacterial community, clinical severity and inflammatory markers in the two most common immune-mediated oral mucosal diseases, namely recurrent aphthous stomatitis (RAS) and oral lichen planus (LP).

Methods: Patients with RAS (n = 15) and LP (n = 18) and healthy controls (n = 13) were recruited using criteria to reduce the effect of factors that influence the microbiota structure independently of oral mucosal disease. Clinical severity was quantified using validated scoring methods.

ODELAM, rapid sequence-independent detection of drug resistance in isolates of .

Antimicrobial-resistant (Mtb) causes over 200,000 deaths each year. Current assays of antimicrobial resistance need knowledge of mutations that confer drug resistance, or long periods of culture time to test growth under drug pressure. We present ODELAM (One-cell Doubling Evaluation of Living Arrays of Mycobacterium), a time-lapse microscopy-based method that observes individual cells growing into microcolonies.

Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.

Background: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy.

Methods: An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA.

Prescription analgesia and adjuvant use by pain severity at admission among nursing home residents with non-malignant pain.

Objective: We estimated the use of prescribed analgesics and adjuvants among nursing home residents without cancer who reported pain at their admission assessment, in relation to resident-reported pain severity.

Methods: Medicare Part D claims were used to define 3 classes of analgesics and 7 classes of potential adjuvants on the 21st day after nursing home admission (or the day of discharge for residents discharged before that date) among 180,780 residents with complete information admitted between January 1, 2011 and December 9, 2016, with no cancer diagnosis.

Results: Of these residents, 27.

Pilchard orthomyxovirus (POMV). II. Causative agent of salmon orthomyxoviral necrosis, a new disease of farmed Atlantic salmon Salmo salar.

Since 2012, an orthomyxo-like virus has been consistently linked to epizootics in marine farmed Atlantic salmon in Tasmania, Australia. Here we describe the properties of the virus, designated the pilchard orthomyxovirus (POMV), in cell culture and present data verifying its direct role in a disease of Atlantic salmon. In infected cells, viral RNA was detectable in both the nucleus and cytoplasm, consistent with the replication cycle of an orthomyxovirus.

Hospital Characteristics Associated with Palliative Care Program Prevalence.

Over the past two decades, the number of hospitals with palliative care has increased significantly. This study analyzes the availability of palliative care in U.S.

Improving Support for Family Caregivers of People with a Serious Illness in the United States: Strategic Agenda and Call to Action.

An estimated 30% of the adult American population are caregivers and many of the people they support live with serious illnesses. Caregivers provide an average of 20 hours of services per week and are heavily involved in assisting with activities of daily living. This input represents considerable economic value to the health care system and to the well-being of communities.

Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2).

Objective: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD).

Methods: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years).

Applications of benchtop NMR in the organic chemistry instructional laboratory.

The instructional organic chemistry laboratory has been substantially improved through the implementation of benchtop NMR analysis. When used in conjunction with unknown reaction components in multi-outcome experiments, NMR analysis transforms the laboratory exercise into an investigative inquiry wherein students elucidate structures for their products and thereby deduce their unknown reaction components. This analytical approach closely models the research laboratory and is a valuable preparatory tool for undergraduate researchers.

Abnormal Vital Signs Predict Critical Deterioration in Hospitalized Pediatric Hematology-Oncology and Post-hematopoietic Cell Transplant Patients.

Hospitalized pediatric hematology-oncology and post-hematopoietic cell transplant (HCT) patients have frequent deterioration requiring Pediatric Intensive Care Unit (PICU) care. Critical deterioration (CD), defined as unplanned PICU transfer requiring life-sustaining interventions within 12 h, is a pragmatic metric to evaluate emergency response systems (ERS) in pediatrics, however, it has not been investigated in these patients. The goal of this study was to evaluate if CD is an appropriate metric to assess effectiveness of ERS in pediatric hematology-oncology and post-HCT patients and if it is preceded by an actionable period of vital sign changes.

Regio- and Enantioselective Synthesis of Trifluoromethyl-Substituted Homoallylic α-Tertiary NH -Amines by Reactions Facilitated by a Threonine-Based Boron-Containing Catalyst.

A method for catalytic regio- and enantioselective synthesis of trifluoromethyl-substituted and aryl-, heteroaryl-, alkenyl-, and alkynyl-substituted homoallylic α-tertiary NH -amines is introduced. Easy-to-synthesize and robust N-silyl ketimines are converted to NH-ketimines in situ, which then react with a Z-allyl boronate. Transformations are promoted by a readily accessible l-threonine-derived aminophenol-based boryl catalyst, affording the desired products in up to 91 % yield, >98:2 α:γ selectivity, >98:2 Z:E selectivity, and >99:1 enantiomeric ratio.

Remotely Sensed Imagery for Early Detection of Respiratory Disease in Pigs: A Pilot Study.

Respiratory diseases are a major problem in the pig industry worldwide. Due to the impact of these diseases, the early identification of infected herds is essential. Computer vision technology, using RGB (red, green and blue) and thermal infrared imagery, can assist the early detection of changes in animal physiology related to these and other diseases.

Western gorilla space use suggests territoriality.

The evolutionary origins of how modern humans share and use space are often modelled on the territorial-based violence of chimpanzees, with limited comparison to other apes. Gorillas are widely assumed to be non-territorial due to their large home ranges, extensive range overlap, and limited inter-group aggression. Using large-scale camera trapping, we monitored western gorillas in Republic of Congo across 60 km.